The development of a questionnaire to assess the attitudes of older people to end-of-life issues (AEOLI)

Objectives: To develop an end-of-life attitudes questionnaire for use in a large community-based sample of older people. Design: Nominal groups and standardization of questions. Participants: Eighteen older people, ten academics and five specialist palliative care health professionals were involved in nominal groups. Thirty older people took part in initial pilot work and a further 50 were involved in reliability testing. Results: A 27-item attitudes of older people to end-of-life issues (AEOLI) questionnaire. Discussion: In modern times, death and dying predominantly occurs among older people and yet we know very little about older people's attitudes to end-of-life care. The AEOLI questionnaire can be used in large scale surveys to elicit attitudes on end-of life issues considered important by older people and health care professionals

Machine Learning in Pain Medicine:An Up-To-Date Systematic Review

Introduction: Pain is the unpleasant sensation and emotional experience that leads to poor quality of life for millions of people worldwide. Considering the complexity in understanding the principles of pain and its significant impact on individuals and society, research focuses to deliver innovative pain relief methods and techniques. This review explores the clinical uses of machine learning (ML) for the diagnosis, classification, and management of pain. Methods: A systematic review of the current literature was conducted using the PubMed database library. Results: Twenty-six papers related to pain and ML research were included. Most of the studies used ML for effectively classifying the patients’ level of pain, followed by use of ML for the prediction of manifestation of pain and for pain management. A less common reason for performing ML analysis was for the diagnosis of pain. The different approaches are thoroughly discussed. Conclusion: ML is increasingly used in pain medicine and appears to be more effective compared to traditional statistical approaches in the diagnosis, classification, and management of pain

Safety, tolerability, and nocebo phenomena during transcranial magnetic stimulation: a systematic review and meta‐analysis of placebo‐controlled clinical trials

Background The methodology used for the application of repetitive transcranial magnetic stimulation (TMS) is such that it may induce a placebo effect. Respectively, adverse events (AEs) can occur when using a placebo, a phenomenon called nocebo. The primary aim of our meta‐analysis is to establish the nocebo phenomena during TMS. Safety and tolerability of TMS were also studied. Methods After a systematic Medline search for TMS randomized controlled trials (RCTs), we assessed the number of patients reporting at least one AE and the number of discontinuations because of AE in active and sham TMS groups. Results Data were extracted from 93 RCTs. The overall pooled estimate of active TMS and placebo treated patients who discontinued treatment because of AEs was 2.5% (95% CI 1.9%‐3.2%) and 2.7% (95% CI 2.0%‐3.5%), respectively. The pooled estimate of active TMS and placebo treated patients experiencing at least one AE was 29.3% (95% CI 19.0%‐22.6%) and 13.6% (95% CI 11.6%‐15.8%), respectively, suggesting that the odds of experiencing an AE is 2.60 times higher (95% CI 1.75‐3.86) in the active treatment group compared to placebo (p < 0.00001). The most common AE was headache, followed by dizziness. Secondary meta‐analyses in depression and psychotic disorders showed that the odds of experiencing an AE is 3.98 times higher (95% CI 2.14‐7.40) and 2.93 times higher (95% CI 1.41‐6.07), respectively, in the active treatment groups compared to placebo. Conclusions TMS is a safe and well‐tolerated intervention. Nocebo phenomena do occur during TMS treatment and should be acknowledged during clinical trial design and daily clinical practice

Psychogenic non-epileptic seizures (PNES) in the context of concurrent epilepsy – making the right diagnosis

Epilepsy is a risk factor for the development of psychogenic non-epileptic seizures (PNES) and comorbid epilepsy is recognized as a comorbidity in about 10–30% of patients with PNES. The combination of epileptic and nonepileptic seizures poses a particular diagnostic challenge. In patients with epilepsy, additional PNES may be suspected on the basis of their typical semiology. The possibility of additional PNES should also be considered if seizures fail to respond to antiepileptic drug treatment, in patients with frequent emergency admissions with seizures and in those who develop new types of seizures. The description of semiological details by patients and witnesses can suggest additional PNES. Home video recordings can support an initial diagnosis, however, especially in patients with mixed seizure disorders it is advisable to seek further diagnostic confirmation by capturing all habitual seizure types with video-EEG. The clinical features of PNES associated with epilepsy are similar to those in isolated PNES disorders and include longer duration, fluctuating course, asynchronous movements, pelvic thrusting, side-to-side head or body movement, persistently closed eyes and mouth, ictal crying, recall of ictal experiences and absence of postictal confusion. PNES can also present as syncope-like episodes with unresponsiveness and reduced muscle tone. There is no unique epileptological or brain pathology profile putting patients with epilepsy at risk of additional PNES. However, patients with epilepsy and PNES typically have lower educational achievements and higher levels of psychiatric comorbidities than patients with epilepsy alone. Psychological trauma, including sexual abuse, appears to be a less relevant aetiological factor in patients with mixed seizure disorders than those with isolated PNES, and the gender imbalance (i.e. the greater prevalence in women) is less marked in patients with PNES and additional epilepsy than those with PNES alone. PNES sometimes develop after epilepsy surgery. A diagnosis of ‘known epilepsy’ should never be accepted without (at least brief) critical review. This narrative review summarises clinical, electrophysiological and historical features that can help identify patients with epilepsy and additional PNES

Oxidative Stress and Memory Decline in Adults with Down Syndrome: Longitudinal Study

By the age of 40, virtually all patients with Down syndrome (DS) have neuropathological changes characteristic of Alzheimer's disease (AD). The aim of our study was to investigate whether the levels of superoxide dismutase enzymes (SOD), glutathione peroxidase (GPx), or their ratio could predict cognitive decline in people with DS over a 4-year period. Thirty-two adults with DS participated in a longitudinal study with SOD and GPx assays at baseline. Informants rated their functional ability and memory function at baseline and at 4 years follow-up. The more able adults with DS also completed assessments of language skills and memory, at two different time points 4 years apart. Twenty-six individuals with DS completed assessments of memory (Modified Memory Object Task, MOMT), adaptive behavior (ABAS), and receptive vocabulary (British Picture vocabulary, BPVS) at both time-points. SOD positively correlated with change on the MOMT score (r = 0.578, p = 0.015). There were no significant correlations between GPx level or SOD/GPx ratio and temporal changes in ABAS, BPVS, or MOMT scores. Our results suggest that SOD predicts memory decline over time and that these antioxidant enzymes could be a potential target for prevention of memory deterioration in adults with DS. Further research is required to test whether supplements which improve SOD function can also prevent cognitive decline. These findings may also have implications for prevention of cognitive decline in other groups which are at high risk of developing dementia, such as adults with familial AD or mild cognitive impairment

Increased oxidative stress as a risk factor in chronic idiopathic axonal polyneuropathy

Chronic idiopathic axonal polyneuropathy (CIAP) is a disorder with insidious onset and slow progression, where no etiology is identified despite appropriate investigations. We aimed to investigate the role of oxidative stress as a risk factor for the pathogenesis of CIAP. Sera of patients with CIAP were tested for protein carbonyl (PC) and 8-hydroxydeoxyguanosine (8H). As a control group, we recruited patients with gluten neuropathy. Twenty-one patients with CIAP and 21 controls were recruited. The two groups did not differ significantly regarding demographics or clinical characteristics (i.e., neuropathy type or disease severity). After adjusting for gender, having CIAP was positively correlated with both the 8H titer (standardized beta coefficient 0.349, p = 0.013) and the PC titer (standardized beta coefficient 0.469, p = 0.001). Oxidative stress appears to be increased in CIAP and might have a role in the pathogenesis of the disease

Ionic lanthanum passage across cerebral endothelium exposed to hyperosmotic arabinose

Hyperosmotic media infused into the cerebral circulation open the blood-brain barrier to protein and colloid. The mechanism whereby such substances cross the affected vessels is still disputed. We describe here the transendothelial route taken by ionic lanthanum (La 3+ ), a small electron-dense tracer which, unlike colloidal lanthanum, can be administered to the living animal. In adult rats, 2.9 ml of hyperosmotic (1.4 M) arabinose was infused into the internal carotid artery as a 30-s bolus, followed by 5 mM LaCl 3 . To find the extravasated La 3+ , which is invisible by light microscopy, horseradish peroxidase (HRP) was injected simultaneously into the femoral vein. The hyperosmotic treatment resulted in exudation of both HRP and La 3+ primarily around cerebral arterioles. The La 3+ crossed arterioles through successive tight junctions between endothelial cells. Although the tight junctions were not discernibly opened, they must have become permeable because the extracellular pools between successive tight junctions were penetrated by the La 3+ . These pools are normally inaccessible to La 3+ . Luminal and abluminal pits and cytoplasmic vesicles, some of them containing La 3+ , formed intraendothelial clusters. Their role, if any, in the transfer of ion remains remains uncertain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47227/1/401_2004_Article_BF00685347.pd

A dementia classification framework using frequency and time-frequency features based on EEG signals.

Alzheimer's Disease (AD) accounts for 60-70% of all dementia cases, and clinical diagnosis at its early stage is extremely difficult. As several new drugs aiming to modify disease progression or alleviate symptoms are being developed, to assess their efficacy, novel robust biomarkers of brain function are urgently required. This study aims to explore a routine to gain such biomarkers using the quantitative analysis of Electroencephalography (QEEG). This paper proposes a supervised classification framework which uses EEG signals to classify healthy controls (HC) and AD participants. The framework consists of data augmentation, feature extraction, K-Nearest Neighbour (KNN) classification, quantitative evaluation and topographic visualisation. Considering the human brain either as a stationary or a dynamical system, both frequency-based and time-frequency-based features were tested in 40 participants. Results: a) The proposed method can achieve up to 99% classification accuracy on short (4s) eyes open EEG epochs, with the KNN algorithm that has best performance when compared to alternative machine learning approaches; b) The features extracted using the wavelet transform produced better classification performance in comparison to the features based on FFT; c) In the spatial domain, the temporal and parietal areas offer the best distinction between healthy controls and AD. The proposed framework can effectively classify HC and AD participants with high accuracy, meanwhile offering identification and localisation of significant QEEG features. These important findings and the proposed classification framework could be used for the development of a biomarker for the diagnosis and monitoring of disease progression in AD

Pain in platin-induced neuropathies: A systematic review and meta-analysis

INTRODUCTION: Platin-induced peripheral neuropathy (PIPN) is a common cause of PN in cancer patients. The aim of this paper is to systematically review the current literature regarding PIPN, with a particular focus on epidemiological and clinical characteristics of painful PIPN, and to discuss relevant management strategies. METHODS: A systematic computer-based literature search was conducted on the PubMed database. RESULTS: This search strategy resulted in the identification of 353 articles. After the eligibility assessment, 282 articles were excluded. An additional 24 papers were identified by scanning the reference lists. In total, 95 papers met the inclusion criteria and were used for this review. The prevalence of neuropathic symptoms due to acute toxicity of oxaliplatin was estimated at 84.6%, whereas PN established after chemotherapy with platins was estimated at 74.9%. Specifically regarding pain, the reported prevalence of pain due to acute toxicity of oxaliplatin was estimated at 55.6%, whereas the reported prevalence of chronic peripheral neuropathic pain in PIPN was estimated at 49.2%. CONCLUSION: Peripheral neuropathy is a common complication in patients receiving platins and can be particularly painful. There is significant heterogeneity among studies regarding the method for diagnosing peripheral neuropathy. Nerve conduction studies are the gold standard and should be performed in patients receiving platins and complaining of neuropathic symptoms post-treatment

Cerebellar ataxia and sensory ganglionopathy associated with light-chain myeloma.

BACKGROUND: Cerebellar ataxia with sensory ganglionopathy is a rare neurological combination that can occur in some hereditary ataxias including mitochondrial diseases and in gluten sensitivity. Individually each condition can be a classic paraneoplastic neurological syndrome. We report a patient with this combination who was diagnosed with light-chain myeloma ten years after initial presentation. CASE PRESENTATION: A 65-year-old Caucasian lady was referred to our Ataxia Clinic because of a 6-year history of progressive unsteadiness and a 2-year history of slurred speech. Past medical history included arterial hypertension. The patient was a non-smoker was not consuming alcohol excessively. There was no family history of ataxia. Neurological examination revealed prominent gaze-evoked nystagmus, heel to shin ataxia, gait ataxia, reduced reflexes and loss of vibration sensation in the legs. Cerebellar ataxia was confirmed using magnetic resonance spectroscopy of the cerebellum and sensory ganglionopathy using neurophysiological assessments including blink reflex study. A muscle biopsy that was arranged to explore the possibility of mitochondrial disease revealed amyloidosis. Urinalysis confirmed the presence of light chains. A bone marrow biopsy confirmed the diagnosis of light chain multiple myeloma. CONCLUSIONS: Whilst it could be argued that this could simply be a coincidence, the rarity of these conditions and the absence of an alternative aetiology for the neurological dysfunction argue in favour of a paraneoplastic phenomenon